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FLASH GENE
Symbol HIF1A contributors: mct/shn/pgu - updated : 09-10-2011
HGNC name hypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)
HGNC id 4910
Location 14q23.2      Physical location : 62.162.118 - 62.214.977
Synonym name
  • member of PAS superfamily 1
  • member of PAS
  • ARNT interacting protein
  • ARNT-interacting protein
  • basic-helix-loop-helix-PAS protein MOP1
  • hypoxia-inducible factor 1 alpha isoform I.3
  • hypoxia-inducible factor 1-alpha
  • PAS domain-containing protein 8
  • class E basic helix-loop-helix protein 78
    • Synonym symbol(s) MOP1, HIF1, PASD8, HIF-1alpha, HIF1-ALPHA, bHLHe78
    DNA
    TYPE functioning gene
    STRUCTURE 52.86 kb     15 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D14S1429 - D14S592 - HIF1A - D14S997 - D14S290 - qter
    Physical map
    FLJ46156 14q23.1 FLJ46156 protein C14orf135 14q23.1 chromosome 14 open reading frame 135 DHRS7 14q23.1 dehydrogenase/reductase (SDR family) member 7 PSMA3P 14 proteasome (prosome, macropain) subunit, alpha type, 3 pseudogene PPM1A 14q22.3-q23.1 protein phosphatase 1A (formerly 2C), magnesium-dependent, alpha isoform RBM8B 14q22.1-q22.3 RNA binding motif protein 8B pseudogene C14orf39 14q23.1 chromosome 14 open reading frame 39 LOC390483 14 similar to sal-like 4 SIX6 14q22.3-q23 sine oculis homeobox homolog 6 (Drosophila) LOC387992 14 LOC387992 SIX1 14q22-q23 sine oculis homeobox homolog 1 (Drosophila) SIX4 14q23 sine oculis homeobox homolog 4 (Drosophila) MNAT1 14q23 menage a trois 1 (CAK assembly factor) MAD2L1P 14 MAD2 mitotic arrest deficient-like 1 (yeast) pseudogene SRMP2 14 spermidine synthase pseudogene 2 SLC38A6 14q23.1 solute carrier family 38, member 6 LOC161291 14q23.1 hypothetical protein LOC161291 PRKCH 14q22-q23 protein kinase C, eta HIF1A 14q21-q24 hypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor) SNAPC1 14q22 small nuclear RNA activating complex, polypeptide 1, 43kDa LOC122867 14q23.1 similar to cytochrome c oxidase subunit IV (COXIV) pseudogene (E.C. 1.9.3.1) MOCS3P 14 molybdenum cofactor synthesis 3 pseudogene SYT14L 14q23.2 synaptotagmin XIV-like LOC390484 14 similar to ATP synthase alpha subunit KCNH5 14q23.1 potassium voltage-gated channel, subfamily H (eag-related), member 5 ADPRTP2 14q24 ADP-ribosyltransferase (NAD+; poly (ADP-ribose) polymerase) pseudogene 2 ARHJ 14q23.1 ras homolog gene family, member J GPB5 14q23.2 glycoprotein beta 5 PPP2R5E 7p12-p11.2 protein phosphatase 2, regulatory subunit B (B56), epsilon isoform LOC390485 14 similar to ribosomal protein L31 GCATP 14q23.2 glycine C-acetyltransferase pseudogene LOC112840 14q23.2 similar to RIKEN cDNA 2600001A11 gene HSPEP2 14 heat shock 10kDa protein 1 (chaperonin 10) pseudogene 2
    RNA
    TRANSCRIPTS type messenger
    text ARE elements in the 3'UTR of mRNA
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 splicing 4082 92.67 826 - 2005 15750626
  • a 15 exons variant
  • encoding for the longer product
    • 14 splicing 3955 82.62 735 - 2005 15750626
  • a 14 exons variant
  • lacking exon 14
    • 15 splicing 3979 - 850 - 2005 15750626
  • lacking both exons 11 and 12
  • protein without ODD domain, TAD and C terminal NLS motif
  • exhibiting neither the activity of transactivation nor hypoxia-induced nuclear translocation
    		•
    EXPRESSION
    Type widely
    constitutive of
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
     vessel   moderately
    Digestiveesophagus   moderately
     mouth   highly
    Lymphoid/Immunethymus   moderately
    Reproductivemale systemtestis  moderately
    Respiratoryrespiratory tracttrachea  predominantly
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connective   highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
     chondrocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal basic helix-loop-helix (bHLH) domain
  • a stretch of approximately 300 amino acids, termed the PAS (Per - ARNT - Sim) domain containing two internal repeats, required for heterodimerization and DNA binding
  • N and C terminal hypoxia-inducible transactivation domains (TADS)
  • a transcriptional inhibitory domain
  • an oxygen-dependent degradation domain (ODD)
    • conjugated PhosphoP , Acetylated
    mono polymer homomer , dimer
    HOMOLOGY
    interspecies ortholog to Hif1a, Rattus norvegicus
    ortholog to Hif1a, Mus musculus
    ortholog to HIF1A, Pan troglodytes
    Homologene
    FAMILY
  • PAS superfamily
    • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • involved (essential) in cardiovascular development and systemic O2 homeostasis
  • essential for the regulation of glycolytic capacity in myeloid cells, has a role in regulation of survival and function in the inflammatory microenvironmen (
  • controlled through stability regulation of its alpha subunit, which is expressed under hypoxia but degraded under normoxia
  • regulating the expression of TWIST1 by binding directly to the hypoxia-response element (HRE) in the TWIST1 proximal promoter
  • promotes glycogen accumulation through regulating PPP1R3C expression under hypoxia, which revealed a novel metabolic adaptation of cells to hypoxia)
  • may be directly or indirectly required for normal development of the retinal vasculature, especially of the intermediate plexus (
  • HIF1A and EPAS1 play a critical role in cellular response to hypoxia
  • opposite roles of HIF1A and EPAS1 in the regulation of IL8 expression in endothelial cells
  • RUNX2, HIF1A, and VEGFA may regulate vascular angiogenesis spatially and temporally in the hypertrophic zone of the growth plate during endochondral bone formation
  • exerts a negative control over beta-cell differentiation
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism carbohydrate
    signaling signal transduction
    a component
  • complexing with HIF2A and HIF2B (ARNT) for activation of genes involved in metabolism, angiogenesis, erythropo
    • esis and glycolysis through the recruitement of the CBP/p300 co-activator
  • heterodimerizing with MOP9
    • INTERACTION
    DNA
  • prostate-specific antigen gene promoter (
    • RNA
    small molecule
    protein
  • dimerize with ARNT (
  • MOP3 (
  • SRC-1 and transcription intermediary factor 2, TIF2 (
  • von Hippel-Lindau tumor suppressor protein, VHL
  • proteasome (prosome, macropain) subunit, alpha type, PSMA7 (
  • tumor suppressor p53 (
  • Jun activation domain-binding protein-1, JAB1
  • period homolog 1 (Drosophila), PER1 (
  • functionally cooperates with c-Jun (
  • p53 binding protein homolog (mouse), MDM2 (
  • Brahma, Brm and Brahma/SWI2-related gene 1, Brg-1 (
  • SMT3 suppressor of mif two 3 homolog 1, SUMO1 (
  • cysteine-histidine-rich 1, CH1 (
  • retinoblastoma protein, pRB (
  • osteosarcoma amplified 9, endoplasmic reticulum lectin, OS9 (
  • pVHL-interacting deubiquitinating enzyme 2, VDU2 (
  • necdin homolog (mouse), NDN (
  • ARD1 (
  • MSF-A (
  • metastasis-associated protein 1, MTA1 (
  • testis specific gene antigen 10, TSGA10 (
  • beta-catenin (
  • Nur77 (
  • spermidine/spermine-N(1)-acetyltransferase 2, SSAT2 (
  • signal transducer and activator of transcription3, STAT3 (
  • RACGAP1 (HIF-1alpha function is negatively affected by its interaction with RACGAP1)
  • Reptin
  • MCM2, MCM5, MCM3 and MCM7
  • HDAC4 regulates HIF1A protein acetylation and stability, via HIF1A N-terminal lysines
  • USP19 interacts with components of the hypoxia pathway including HIF1A and rescues it from degradation independent of its catalytic activity
    • cell & other
    REGULATION
    activated by p42/p44 MAPK (
    induced by hypoxia-inducible
    inhibited by p14ARF
    MCM3 (
    valproic acid and trapoxin (
    Other rapidly degraded by proteasome under normoxic conditions
    regulated by von Hippel-Lindau tumour suppressor protein, VHL (
    targeted by VALand
    pVHL-interacting protein functions as a negative regulator of HIF-1alpha transactivation (
    HIF-1&
    945; protein levels downregulated by MCM7 (
    regulated by proteasome (prosome, macropain) subunit, alpha type, 7, PSMA7 (
    PARP1 as a transcriptional coactivator of HIF-1-dependent gene expression during tumor progression (
    epigenetic regulation of CD34 and HIF1A expression during the differentiation of mast cells
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Hif1a-/- mouse embryos with complete deficiency of HIF-1alpha due to homozygosity for a null allele at the Hif1a locus die at midgestation, with multiple cardiovascular malformations and mesenchymal cell death (
  • transgenic mice expressing constitutively active HIF-1alpha in epidermis displayed hypervascularity with 66% increase in dermal capillaries, a 13-fold elevation of total vascular endothelial growth factor (VEGF) expression, and a six- to ninefold induction of each VEGF isoform (
  • partialHIF-1 alpha deficiency has a dramatic effect on carotid body neural activity and ventilatory adaptation to chronic hypoxia in Hif1a(+/-) mice (
  • neural cell-specific HIF-1alpha-deficient mice exhibit hydrocephalus accompanied by a reduction in neural cells and an impairment of spatial memory (
  • skeletal-muscle HIF-1alpha knockout mice have an altered exercise endurance (
  • mice lacking HIF-1alpha in their myeloid cell lineage showed decreased bactericidal activity and failed to restrict systemic spread of infection from an initial tissue focus (
  • mice lacking HIF-1alpha in osteoblasts had impaired angiogenesis and bone healing (
  • HIF-1alpha- and TWIST-null mice show similarities in their phenotypes (Yang, 2008)